Journal Article

CANCER BIOLOGY: Reversibility of promoter induced hepatic focal lesion growth in mice

Kyle L. Kolaja, Donald E. Stevenson, Earl F. Walborg and James E. Klaunig

in Carcinogenesis

Volume 17, issue 7, pages 1403-1409
Published in print July 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.7.1403
CANCER BIOLOGY: Reversibility of promoter induced hepatic focal lesion growth in mice

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The effect of cessation of phenobarbital and dieldrin treatment on hepatic focal lesion growth in male B6C3F1 mice was investigated. Following induction of lesions by diethylnitrosamine, mice were placed on control NIH-07 diet (control diet) or NIH-07 diet containing either dieldrin (10.0 mg/kg diet) or phenobarbital (500 mg/kg diet). Mice were sacrificed after 30 and 60 days of dietary treatment Two additional groups of mice were fed either the dieldrin-or phenobarbital-containing diet for 30 days followed by feeding of NIH-07-only diet for an additional 30 days. The effect of treatment and removal of dieldrin or phenobarbital on lesion growth was examined by measuring both the number of focal lesions per liver and the relative volume of focal lesions. In addition, the rate of cell proliferation and programmed cell death in focal lesion growth was investigated by examining DNA synthesis and apoptosis in the focal lesions. Dietary dieldrin or phenobarbital increased the number of focal lesions and the focal lesion volume. In both dieldrin- and phenobarbital-treated mice, an increased number of eosinophilic lesions were seen. The focal lesion volume was increased in both eosinophilic and basophilic lesions. Dieldrin and phenobarbital treatment also increased the DNA synthetic labeling index in both eosinophilic and basophilic lesions. Removal of dieldrin or phenobarbital from the diet after 30 days of promoter treatment decreased the total number and volume of hepatic focal lesions. The labeling index of the focal lesions was also decreased in these mice. At the terminal sacrifice, the percentage of apoptotic cells in focal lesions was higher in mice fed dieldrin- or phenobarbital-containing diets for the entire 60 days than in mice returned to control diet for the last 30 days. Eosinophilic lesions were more dependent on the presence of a promoting stimulus than the basophilic lesions. These data indicate that induction and maintenance of the growth of some preneoplastic lesions in the mouse may be dependent upon continuous tumor promoter treatment.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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